SI Motility&Secretion

Question 1

What are features of the Duodenum?

Answer 1

25cm length
- Not attached to mesentery → more motility and free movement

Mixes chyme with:
- Pancreatic digestive juices
- Liver secretions
- Intestinal secretions
→ Starts the process of digestion + neutralizes the acidic chyme from the stomach

Parts/Structures:
- Spincter of Oddi → controls secretion from the liver and pancreas
- Intestinal Glands (entrokinase)
- Crypts of Lieberkuhn (invaginations)
- Villi

Question 2

How long and wide is the SI?

Answer 2

6.5 meters long
3.5-cm diameter

Question 3

What are features of the Jejunum and the Ileum compared to the duodenum?
How long?
Where to is start/end?
Diameter?

Answer 3

Jejunum → 2.5m length
Ileum → 3.75m length
*no anatomical separation

• Ends at the Ileaocecal junction (Ileocecal spincter)
• Diameter is smaller than duodenum
• Muscular wall → thinner wall and fewer folds than duodenum
• Fewer and smaller villi
• Peyer’s patches (2ndary lymphoid organs in Ileum)
• Attached to mesentery
  Site of digestion & absorption

Question 4

What cells/secretions mainly control secretion and motility during intestinal phase of digestion?

Answer 4

After a acid rich meal (high protein meal):
S cells respond to high acid in the duodenum → Secretin → increase alkaline secretions from ductal cells

After a fatty meal:
I cells responds to presence of fat → CCK secretion → increase pancreatic, gallbladder secretions → pancreatic lipases and bile salts emulsify the fats and form micelles

CCK and Secretin → stomach relaxation to decrease the movement of contents forward

Question 5

what vessel supplies blood to villus of SI?
What is it regulated by?

Answer 5

Superior Mesenteric Artery ~ 10% of cardiac output

Blood flow increase ~50-300% during a meal to maintain the concentration gradient

Controlled by nerves, hormones and local paracrine factors
- parasympathetic system → vasodilation & increased blood flow
- Blood drains into the hepatic portal vein

Question 6

Where do lipids go when they are absorbed by enterocytes?

Answer 6

Lipids go from enterocytes to the Lacteals → the lymphatic vessels of the small intestine which absorb digested fats

Muscular contraction at SI helps move fats from the lacteals (to maintain concentration gradient in the enterocytes)

Question 7

What are 3 functions of motility in the small intestine?

Answer 7

1) Mixing chyme and digestive juices from liver and pancreas (for them to come in contact with each other)
2) Putting nutrients in contact with absorptive cells
3) Moving stomach contents to the colon

Question 8

What are the 2 types of motility in the SI?

Answer 8

Spontaneous Contractions:
- During a meal
- Due to uneven amplitude of the BER (not enough on its own)
- Influenced by ACh and distension
- 8-12x minute during fed state (12 in duodenum → 8 in the Ileum)

Migrating Myoelectric Complex (MMC):
- In absence of a meal
- cycles of smooth contraction (peristaltic waves) every 1.5 hours lasting ~10 min
- begins in stomach and migrates ‘aborally’ toward colon
- triggered by motilin → produced by M cells in duodenum and jejunum
- Moves the constant secretions fown the GIT or stuck components

Question 9

What is an effect of the change in BER along the SI?

Answer 9

Duodenum = 12/min
Ileum = 8/min

This moves the contents slowly forward towards the colon

*Also change in musculature which is thicker at the level of the duodenum

Question 10

What are different factors that control motility in the intestines?

Answer 10

1. Stretch
2. Enteric Nervous System
3. Extrinsic autonomic nerves (Sympathetic & Parasympathetic)
4. Circulating hormones (motilin)

Question 11

Which 2 reflexes are important for controling motility in the intestines?

Answer 11

1) Myenteric Reflex (local distension)
Food in SI → Contraction of smooth muscle behind the bolus, relaxation ahead of the bolus → Move food along the SI

2) Gastro-ileal Reflex
Food in the stomach → Increase Ileum motility → Relaxation of Ileocecal Spincter
**Gastrin
- This is how we move contents to the colon

Question 12

What different cells found in the villi and crypts of Lieberkühn?

Answer 12

Villi region → Absorption
- Mostly enterocytes
- Some Goblet cells
- Some enteroendocrine cells

Crypts of Lieberkühn → Secretion & Proliferation
- Goblet cells in the higher part
- Enteroendocrine cells in the higher part
- Paneth cells → Antimicrobial peptides (stimulated by PAMPs)
*Secrete Succus Entericus

Proliferative zone in the bottom → Crypt Base Columnar cells producing

Question 13

What are the different cells derived from Intestinal Stem Cells?

Answer 13

*ISCs = Crypt Base Columnar cells
ISCs → Absorptive Progenitors → Enterocytes (absorption of ions, water, nutrients + transport of IgA into SI lumen)

ISCs → Secretory Progenitors → Paneth cells / Enteroendocrine cells / Goblet cells / Tuft cells

Question 14

What are the different type of Enteroendocrine cells derived from ISCs → Secretory progenitors in the GIT?

Answer 14

I cells → CCK
G cells → Gastrin
ECL cells → Histamine
S cells → Secretin

Question 15

What are Label-Retaining Cells (LRC)?

Answer 15

They are intestinal Stem cells in the proliferation zone of the crypts of Lieberkühn which are in a quiescent state

They can be re-activated if the CBC stem cells are lost to help re-populate the crypts and villi

Ex: Activated in chemotherapy because chemo targets rapidly dividing cells → CBC stem cells, but not these LRC

Question 16

What are the different zones of the Crypts of Lieberkühn?

Answer 16

Stem cell Zone (very base)
- ISCs proliferate and secrete succus entericus

Differentiation zone at the top of the Stem Cell Zone → Cells chose a faith

Transit Amplifying Zone
- Cells divide/expand into many cells of their given faith

Question 17

What are the 2 most common ways of absorption of nutrients through the GIT?

Answer 17

1) Slow rates → PASSIVE diffusion
*Most common

2) Faster rates → Facilitated diffusion which relies on active transport of other ions

Question 18

How are starches digested?

Answer 18

1. Amylases from pancreas (1st one in the saliva) break down starches into di/tri-peptides
   - Glucose, Maltose
2. Enzymes in brush border further break peptides down to single molecules
   - Maltase
   - Sucrase
   - Lactase

Question 19

What is SGLT1?

Answer 19

Facilitated diffusion on the apical side of enterocytes
Absorbs 1 Glucose/galactose + 2Na+ (with water by osmosis) from the lumen into enterocytes

*Depends on Na/K ATPase
SGLT = Sodium Glucose Tranpsorter 1

Question 20

What transport makes enterocytes energetically active?

Answer 20

Na/K ATPase (Na+ out, K+ in)

*Facilitated transport requires this pump to maintain concentration gradient

Question 21

What are the main steps of protein digestion?

Answer 21

1. Intestinal lumen → pancreatic enzymes
   - Trypsin, Chymotrypsin, Carboxypeptidases, Elastase
   - Proteins → Oligopeptides
2. Brush border
   - Oligopeptides → di-/tripeptides
3. Enterocytes
   - Absorbed as di-/tri-peptides with H+ ion (cotransport)
   - Factilitated transport
   - Relies on NHE3 exchanger (H+ out / Na+ in) to maintain concentration gradient + Na/K ATPase
   - Inside enterocytes, borken down into amino acids and transported as AA on the basolateral side to circulation

Question 22

What are the steps of lipid absorption from the lumen, through enterocytes, to circulation?

Answer 22

1. Micelle formation in the lumen
2. Transport across the apical enterocyte membrane
3. Incorporation into lipid droplets (inside enterocytes)
4. Transport to ER → Chylomicron formation → soluble for absorption via lymphatic system
5. Exocytosis to lymphatics

Question 23

How is iron absorbed by enterocytes?

Answer 23

Fe2+ is absorbed via endocytosis and packaged into Ferritin micells or packaged to the blood stream
*We ingest Fe3+, so needs to be converted

Question 24

How does B12 keep its integrity all along the process of absorption?

Answer 24

1. R-factors in saliva bind to it to protect it
2. Intrinsic factors in the stomach bind to it to protect it
3. Receptor in the distal Ileum bind B12-IF-IF-B12 complex → B12 is sent to circulation
4. B12 is bound by transcobalamin to protect it in the blood

Question 25

What causes symptoms in patients infected with Vibrio cholerae?

Answer 25

Produces a Vibrio cholerae toxin (84 000 kDa protein) 1. Binds to Gm1 receptor in brush border 2. Activates adenyl cyclase with increase in cAMP 3. Activates CFTR Cl- channels → efflux of Cl- into intestinal lumen → increased secretion of Na+, water follow to the SI lumne 4. Massive secretion of water and electrolytes **Massive dearrhea

Question 26

Why do we treat Cholera patients with oral fluid or IV containing NaCl and glucose + Tetracycline?

Answer 26

Treat them with a solution isotonic with plasma (NaCl + Glucose) → SGLT1 transporter will allow entry inside the cell with water following by osmosis → helps with dehydration → Avoids dehydration, hypovolemia, renal failure and death Tetracycline → antibiotic drug → kill Cibrio cholerae

Question 27

Are changes in intestinal motility involved in cholera?

Answer 27

Distension of the intestine by high volumes of fluid → stimulates peristaltic activity which normally isn't present in the SI

Question 28

What are the main features of the colon anatomy? Main functions?

Answer 28

Length = 1.5m (shorter than SI) Diameter = 6 cm (larger than SI) 1. Ceacum, where appendix connects 2. Ascening colon 3. Transverse colon 4. Descending colon 5. Sigmoid colon 6. Rectum 7. Internal anal sphincter (smooth muscle) 8. Anal column 9. External anal sphincter (striated muscle)

Question 29

What are the main functions of the colon?

Answer 29

- Absorb water & electrolytes - Store fecal material & release it to the external environment - Produce mucous → facilitate movement + help fecal particles adhere - Provide envrionment for bacteria

Question 30

What is the general wall structure of the colon? What are the 4 layers?

Answer 30

No villi, Only crypts - Not much absorption, mostly secretions - APUD cells → endocrine function - Goblet cells → mucous 4 layers: 1. Mucosa 2. Submucosa 3. Muscularis External (Inner circular layer + longitudinal muscle layer) 4. Serosa

Question 31

Is more water absorbed in the SI or in the colon?

Answer 31

More water is absorbed in the SI (850mL/day) by osmosis with the nutrients and ions Less in the colon because less absorption of other stuff (350mL/day), by osmosis with electrolytes/ions

Question 32

Which channels are important for secretion and absorption in the colon?

Answer 32

Net secretion of K+ (through junctions) and HCO3- (in exchange for Cl-) Cells have apical NHE3 (H+ out / Na+ in) + basolateral Na+/K+ ATPase (Na+ out) to maintain concentration gradient Water flows through junctions by osmosis

Question 33

What 4 factors regulate secretions in the colon?

Answer 33

1. Distension 2. Irritation of walls (by undigested fibers) 3. Neuronal inputs (Enteric NS and Autonomic NS) 4. Hormones

Question 34

What nervous inputs stimulate vs inhibit secretions in the colon?

Answer 34

Parasympathetic → Stimulation: - ACh & VIP Sympathetic → Inhibition: - Adrenaline & Somatostatin

Question 35

What are important features of the microbiota in the GIT tract? Where? Role?

Answer 35

1. Stomach and SI are almost sterile (no microbes, except in the case of H. pylori infections → ulcers) 2. Most bacteria found in the colon, the other side of the Ileoceacal sphincter 3. Bacteria are mostly anaerobic and rod shaped Major functions: - Synthesize B-complex and K vitamins → lipid soluble so can diffuse into cells - Convert primary bile acids to 2ndary bile acids → excretion (less soluble, minority of bile acids) - Deconjugate bilirubin → excretion

Question 36

What are the different fibers of parasympathetic inputs to colon innervation?

Answer 36

1. Vagus nerve → Proximal colon (and rest of GIT) 2. Pudendal nerve → Distal colon - Similar sensory re-inforcement reflex

Question 37

What are sources/mechanisms of colon motility?

Answer 37

Distension: - Mixing → slow, segmenting, uncoordinated contraction - Propulsion → peristalsis or sequential haustration (contraction of a few haustre), 5-10 cm/hour (slow) Irritation of the colon wall: - 'fiber' in the diet provokes distension & stimulates mechanoreceptors (help keep more water to prevent constipation) - Laxatative activate chemoreceptors in the colon to stimulate motility (ex: senna)

Question 38

What are extrinsic and intrinsic sources of nervous motility control in the colon?

Answer 38

Extrinsic parasympathetic → pudendal nerves (mostly controls external anal sphincter, somatic) Intrinsic enteric nervous system → Intramural plexi & muscularis mucosa

Question 39

What is the stimulus and responses of the defecation reflex?

Answer 39

*Involuntary Mass movement → increased activity in sigmoid colon - Stimulus = distension in rectum Response: - Contraction in rectum (reflex du to its distension), sigmoid colon - Relaxation of internal anal sphincter - Contraction of external anal sphincter These responses lead to increased pressure in rectum

Question 40

What are physiological factors involved in delay vs defecation following increased pressure in rectum?

Answer 40

1. Defecation - voluntary relaxation of external anal sphincter - Relaxation of puborectalis muscle - Forward peristalsis in rectum, sigmoid colon - Valsalva maneuver (increases abdominal pressure) 2. Delay - Contraction of external anal sphincter - Contraction of puborectalis muscle - Reverse peristlasis in rectum (move contents back up → allows further water reabsorption → constipation) - If done too often, weakens defecation reflexes

Question 41

What are the 3 defecation reflex controls?

Answer 41

1. Primary Reflex → ENS 2. Reinformcement → Parasympathetic reflex 3. Conscious control → loop back to the cortex (for opening of the external anal sphincter)

Question 42

What is Hirschsprung's disease? Cause/Symptoms *also called congenital megacolon

Answer 42

Cause: Absence of ENS excitatory and inhibitory neurons are absent → Lumen narrows due to tonic contraction → Fecal material accumulates, but does not signal defecation (no reflex) *No reflex relaxation of internal anal sphincter is impared, distal colon becomes distended Symptoms: - Very little meconium *Meconium = 1st feces, full of RBC hemolysis product - Distended abdomen - Obstruction was liberated manually by doctor, but re-occured Solution: surgically remove the section which lack innervation

Question 43

In Hirschsprung's disease, why was it necessary to resect part of the large intestine?

Answer 43

The response to distention of the rectum (relaxation of the internal anal sphincter) is diminished The internal anal sphincter remains contracted due to direct parasympathetic stimulation

Question 44

Which parts of the GIT have the largest diameter?

Answer 44

Stomach and Colon

Question 45

Where is cholesterol absorbed the GIT is absorbed? What is its purpose?

Answer 45

Cholesterol is absorbed along the small intestine → raw material for bile salts